Nicholls J, Hourani S M O, Hall J M
School of Biomedical and Life Sciences, University of Surrey, Guildford, Surrey, UK.
Auton Autacoid Pharmacol. 2002 Aug;22(4):209-14. doi: 10.1046/j.1474-8673.2002.00259.x.
1 The aim of this study was to characterize the adenosine receptor mediating vasodilation in the microvasculature of the hamster cheek pouch in vivo. A range of adenosine agonists was used including N6-cyclopentyladenosine (CPA) (A1 agonist), 5'-N-ethylcarboxamidoadenosine (NECA) (non-selective), 2-chloroadenosine (2CADO) (non-selective), 2-p-(2-carboxyethyl)-phenethylamino-5'-N-ethylcarboxamidoadenosine (CGS 21680) (A2A agonist), N6-(3-iodobenzyl)-adenosine-5'-N-methyluronamide (IBMECA) (A3 agonist) and adenosine, as well as the adenosine antagonists 8-sulphophenyltheophylline (8-SPT) (A1/A2 antagonist), 1,3-dipropyl-8-cyclopentylxanthine (DPCPX) (A1 antagonist) and 4-(2-[7-amino-2-(2-furyl)[1,2,4]-triazolo[2,3-a][1,3,5]triazin-5-ylamino]ethyl)phenol (ZM 241385) (A2A antagonist). 2 All the adenosine analogues used induced vasodilation at concentrations between 10 nm and 1 microm, and the potency order was NECA > CGS 21680 > 2CADO > CPA=IBMECA >> adenosine, indicating an action at A2A receptors. 8-SPT (50 microm) antagonized vasodilator responses to NECA with an apparent pKB of 5.4, consistent with an action at A1 or A2 receptors and confirming that A3 receptors are not involved in this response. 3 DPCPX (10 nm) had no effect on vasodilation evoked by NECA, suggesting that this response was not mediated via A1 receptors, while ZM 241385 (10 nm) antagonized dilator responses to NECA with an apparent pKB of 8.9 consistent with an action via A2A receptors. 4 Overall these results suggest that adenosine A2A receptors mediate vasodilation in the hamster cheek pouch in vivo.
1 本研究的目的是在体内对介导仓鼠颊囊微血管舒张的腺苷受体进行特性描述。使用了一系列腺苷激动剂，包括N6-环戊基腺苷（CPA）（A1激动剂）、5'-N-乙基甲酰胺基腺苷（NECA）（非选择性）、2-氯腺苷（2CADO）（非选择性）、2-p-(2-羧乙基)-苯乙氨基-5'-N-乙基甲酰胺基腺苷（CGS 21680）（A2A激动剂）、N6-(3-碘苄基)-腺苷-5'-N-甲基脲酰胺（IBMECA）（A3激动剂）和腺苷，以及腺苷拮抗剂8-磺苯基茶碱（8-SPT）（A1/A2拮抗剂）、1,3-二丙基-8-环戊基黄嘌呤（DPCPX）（A1拮抗剂）和4-(2-[7-氨基-2-(2-呋喃基)[1,2,4]-三唑并[2,3-a][1,3,5]三嗪-5-基氨基]乙基)苯酚（ZM 241385）（A2A拮抗剂）。2 所使用的所有腺苷类似物在10纳米至1微米的浓度范围内均能诱导血管舒张，其效力顺序为NECA > CGS 21680 > 2CADO > CPA = IBMECA >> 腺苷，表明作用于A2A受体。8-SPT（50微米）拮抗对NECA的血管舒张反应，表观pKB为5.4，这与作用于A1或A2受体一致，并证实A3受体不参与此反应。3 DPCPX（10纳米）对NECA诱发的血管舒张无影响，表明该反应不是通过A1受体介导的，而ZM 241385（10纳米）拮抗对NECA的舒张反应，表观pKB为8.9，这与通过A2A受体的作用一致。4 总体而言，这些结果表明腺苷A2A受体在体内介导仓鼠颊囊的血管舒张。
